• Journal of Yeungnam Medical Science
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• v.23 no.2
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• pp.143-151
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• 2006

In the past decade, the median duration of survival among patients with advanced colorectal cancer has increased from 12 months to about 18 months, primarily as a results of the introduction of irinotecan and oxaliplatin. Advances in the understanding of the molecular mechanisms underlying the development and progression of cancer have resulted in the discovery of new therapeutic interventions that target specific molecular abnormalities. Their specificity, and therefore their potential to bind preferentially and modify tumor-specific targets, sparing normal tissues and causing fewer side-effects compared to conventional cytotoxic agents, makes them an attractive therapeutic option. The future of this approach for the treatment of solid tumors is promising.

• Journal of Digestive Cancer Research
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• v.2 no.2
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• pp.52-55
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• 2014

The incidence of colorectal cancer (CRC) has continuously increased and CRC is a major cause of cancer-related death. Systemic chemotherapy has resulted in a significant improvement in overall survival in metastatic CRC. The development of biologic agents for the treatment of CRC has additionally expanded the options for the treatment. Cetuximab is useful in KRAS wild type tumors in combination with chemotherapy for metastatic disease in both the first and second line settings. It is also used as monotherapy after failure of both irinotecan and oxaliplatin containing regimens. Panitumumab has similar indications, and is primarily used in patients intolerant to cetuximab due to hypersensitivity reactions. Bevacizumab is primarily used as first line and second line therapy in metastatic CRC. However, the optimal way and duration to combine these chemotherapeutic agents are not yet established.

• Nutrition Research and Practice
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• v.16 no.2
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• pp.161-172
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• 2022

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133⁺CD44⁺ HCT116 and CD133⁺CD44⁺ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133⁺CD44⁺ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133⁺CD44⁺ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1851-1855
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• 2015

Background: There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. Materials and Methods: The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). Conclusions: Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior.

• BMB Reports
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• v.50 no.8
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• pp.391-392
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• 2017

Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific roles in colorectal cancer (CRC) progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/Tankyrase (TNKS) interaction mediates survival of adenomatous polyposis coli (APC)-mutant CRC cells was explored. In mice with an inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduced intestinal adenomatous polyposis and thereby increased survival. In APC-mutant human CRC cells, PrxII depletion hindered PARP-dependent Axin1 degradation through TNKS inactivation. $H_2O_2-sensitive$ Cys residues in the zinc-binding domain of TNKS1 was found to be crucial for PARsylation activity. Mechanistically, direct binding of PrxII to ARC4/5 domains of TNKS conferred vital redox protection against oxidative inactivation. As a proof-of-concept experiment, a chemical compound targeting PrxII inhibited the growth of tumors xenografted with APC-mutation-positive CRC cells. Collectively, the results provide evidence revealing a novel redox mechanism for regulating TNKS activity such that physical interaction between PrxII and TNKS promoted survival of APC-mutant colorectal cancer cells by PrxII-dependent antioxidant shielding.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3427-3430
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• 2012

Aim: The significance of the mucinous adenocarcinoma in TNM staging and prognosis for colorectal tumor patients is still controversial. The aim was to provide a meta-analysis for TNM staging and prognostic features of colorectal tumors. Methods: 30 individual case-control studies were finally included into this meta-analysis, involving a total of 444,489 cancer cases and 45,050 mucinous adenocarcinomas, of relations with TNM staging and prognostic features. Results: Compared to non-mucinous adenocarcinoma patients, the TNM IV stage accounted for a larger percentage of mucinous adenocarcinomas (OR=1.48, 95%CI 1.28-1.71, POR<0.001) and the prognosis was significantly poor (HR=1.06, 95%CI 1.04-1.08, P<0.001). After heterogeneity testing, the results was similar to the holistic approach outcome (HR=1.48, 95%CI 1.35-1.62, P<0.001). Conclusion: Compared to patients with non-mucinous adenocarcinomas, mucinous adenocarcinoma patients with later TNM staging make up a big percentage, and mucinous adenocarcinoma is an independent risk factor for poor prognosis.

• Clinical Endoscopy
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• v.56 no.4
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• pp.423-432
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• 2023

Compared to endoscopic mucosal resection (EMR), colonoscopic endoscopic submucosal dissection (C-ESD) has the advantages of higher en bloc resection rates and lower recurrence rates of colorectal neoplasms. Therefore, C-ESD is considered an effective treatment method for laterally spread tumors and early colorectal cancer. However, C-ESD is technically more difficult and requires a longer procedure time than EMR. In addition to therapeutic efficacy and procedural difficulty, safety concerns should always be considered when performing C-ESD in clinical practice. Bleeding and perforation are the main adverse events associated with C-ESD and can occur during C-ESD or after the completion of the procedure. Most bleeding associated with C-ESD can be managed endoscopically, even if it occurs during or after the procedure. More recently, most perforations identified during C-ESD can also be managed endoscopically, unless the mural defect is too large to be sutured with endoscopic devices or the patient is hemodynamically unstable. Delayed perforations are quite rare, but they require surgical treatment more frequently than endoscopically identified intraprocedural perforations or radiologically identified immediate postprocedural perforations. Post-ESD coagulation syndrome is a relatively underestimated adverse event, which can mimic localized peritonitis from perforation. Here, we classify and characterize the complications associated with C-ESD and recommend management options for them.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1917-1921
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• 2012

Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients. Methods: Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip. Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues. Conclusions: Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.

• Clinical Endoscopy
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• v.55 no.1
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• pp.15-21
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• 2022

Endoscopic submucosal dissection (ESD) is the standard treatment method for esophageal, gastric, and colorectal cancers. However, it has not been standardized for duodenal lesions because of its high complication rates. Recently, minimally invasive and simple methods such as cold snare polypectomy and underwater endoscopic mucosal resection have been utilized more for superficial nonampullary duodenal epithelial tumors (SNADETs). Although the rate of complications associated with duodenal ESD has been gradually decreasing because of technical advancements, performing ESD for all SNADETs is unnecessary. As such, the appropriate treatment plan for SNADETs should be chosen according to the lesion type, patient condition, and endoscopist's skill.

• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.83-88
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• 2018

Purpose: Double primary colorectal cancer (CRC) and gastric cancer (GC) represent the most common multiple primary malignant tumors (MPMT) in Korea. The recognition and screening of hidden malignancies other than the primary cancer are critical. This study aimed to investigate the clinicopathologic characteristics and survival rates in patients with synchronous or metachronous double primary CRC and GC. Methods: Between January 1994 and May 2018, 11,050 patients were diagnosed with CRC (n=5,454) or GC (n=5,596) at Gil Medical Center. MPMT and metastatic malignant tumors were excluded from this study. A total of 103 patients with double primary CRC and GC were divided into two groups: the synchronous group (n=40) and the metachronous group (n=63). The incidence, clinicopathologic characteristics, and survival rate of the two groups were analyzed. Results: The incidence of synchronous and metachronous double primary CRC and GC was 0.93%. Double primary CRC and GC commonly occurred in male patients aged over 60 years with low comorbidities and minimal previous cancer history. There were significant differences between the synchronous and metachronous groups in terms of age, morbidity, and overall survival. Metachronous group patients were 6 years younger on average (P=0.009), had low comorbidities (P=0.008), and showed a higher 5-year overall survival rate (94.8% and 61.3%, P<0.001) in contrast to synchronous group. Conclusion: When primary cancer (CRC or GC) is detected, it is important to be aware of the possibility of the second primary cancer (GC or CRC) development at that time or during follow-up to achieve early detection and better prognosis.